Direct introduction of exogenous genes into pre-existent tumors could provide an effective therapeutic approach for treatment of localized tumors. In this report we show that direct intratumoral delivery in animals of a replication-deficient adenovirus vector harboring the murine interleukin (IL)-2 gene (AD-mIL2) causes complete disappearance of P815 murine mastocytoma tumors in up to 75% of cases. Histological analysis of treated tumors revealed the presence of several zones of necrosis and the infiltration of macrophages and T cells. Moreover, the successfully treated animals develop a long lasting state of immunity during which further challenges with the tumor cells are rejected. To our knowledge this is the first successful in vivo treatment of an established tumor using adenoviral gene therapy methods.